Dysregulation of calcium in Alzheimer's disease

Abstract

Multiple efforts has underlined importance of calcium dependent cellular processes in the biochemical characterisation of Alzheimer's disease (AD), suggesting that abnormalities in calcium (Ca²⁺) homeostasis might be involved in the pathophysiology of the disease. Studies of the pathogenic mutations in presenilins 1 and 2 (PS1 and PS2) and amyloid precursor protein (APP) responsible for early onset familial AD have estabilished central roles for perturbed cellular Ca²⁺ homeostasis. Studies of apolipoprotein E (ApoE) neurotoxic effects in AD confirmed involvement of Ca²⁺-mediated mechanisms. Futher consequences of Ca²⁺ alterations in AD underline the importance of the ER and mitochondria as the regulatory sites involved in the pathogenesis of neuronal degeneration. Alterations of Ca²⁺ homeostasis include cells from peripheral tissues, including lymphocytes and fibroblasts from AD donors.